Avaliação dos mecanismos envolvidos nos efeitos dos ácidos graxos ômega-3 sobre as complicações associadas ao câncer : uma investigação farmacológica e bioquímica

Abstract

Omega-3 fatty acids display anti-inflammatory and pro-resolution properties, being important allies to the treatment of chronic diseases, such as cancer and its complications. Omega-3 can be employed either for preventing the tumour progression or to manage the chemotherapy side effects. The first part brings a critical review about the protective effects of omega-3 fatty acids in cancer-associated complications, such as pain, depression, anorexia-cachexia syndrome, and paraneoplastic syndrome. Overall, the use of these fatty acids in cancer patients that develop complications seems a very interesting approach; however, there is a lack of clinical evidence regarding the use of omega-3 in these patients. The second part presents data from an in vivo study that investigated the role of free fatty acid receptors, FFA1 and FFA4, in a mouse model of lung cancer cachexia. As pharmacological strategies, the naturally occurring ligands α-linolenic acid (ALA) and docosahexaenoic acid (DHA), the synthetic dual FFA1/FFA4 agonists GW9508 and TUG891, or the selective FFA1 GW1100 or FFA4 AH7614 antagonists, were administered parenterally to LLC-bearing mice, from seven to 21 days after tumour implantation. The induction of cachexia led to an upregulation of FFA1 receptors in skeletal muscle and adipose tissue. The dual FFA1/FFA4 agonist GW9508 promoted beneficial effects associated to adiposity, inflammation, behavioural deficits, and central alterations in these animals, besides reducing the tumour growth. Remarkably, GW9508 has a 100-fold higher affinity for FFA1 receptors, partly explaining the superior effects in comparison with TUG891. Moreover, part of ALA and DHA effects are mediated by the activation of FFA1 and FFA4 receptors, although additional mechanisms cannot be overlooked. It is possible to conclude that the use of omega-3 fatty acids remains an important tool in cancer treatment and that FFA1/FFA4 receptors emerge as attractive pharmacological targets for cancer cachexia management.